The results of detailed genetic studies with Bailey recombinant-inbred (RI) strains of mice have shown that multiple genes, acting in a complementary and independent manner, influence the capacity of mice to give an antibody response to Type III pneumococcal polysaccharide (SSS-111). The high (near 50%) frequency of unique or recombinant phenotyped observed suggests that these genes may be located on different chromoxomes. Support for this view was derived from studies using other RI strains. The genes involved, which tentatively have been assigned to chromosomes 17, 9 and 4, as well as he H-8, H-17, H-20, and G-28 loci, appear to be specific for the antibody response to SSS-111.